Radioimmunotherapy of Solid Tumors: Searching for the Right Target
Hong Song and George Sgouros
Affiliation: Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21231, USA.
Keywords: Radioimmunotherapy, radiolabeled antibody, solid tumor, antigen, non-Hodgkins, lymphoma, Zevalin, 131I tositumomab, Bexxar, Trastuzumab, Cetuximab, Panitumumab, Bevacizumab, DNA single strand breaks, double strand breaks, relative biological effectiveness, antibody dependent cellular cytotoxicity, complement dependent cytotoxicity, Rituximab, Tositumomab, Carcinoembryonic Antigen, Labetuzuma, Mucin 1, Tenascin-C, Ketoconazole, vincristine, Doxorubicin, Filgrastim, Carbonic Anhydrase Isotype IX, Prostate-Specific Membrane Antigen, Ganglioside 2, Epidermal Growth Factor, DNA/histone H1 Associated Protein, Melanin, Tumor Associated Glycoprotein, Mesenchymal Epithelial Transition Factor, Hepatocyte Growth Factor Receptor, anti-neuropilin, tumor endothelial marker 1, 51 integrin, v3 integrin, epidermal growth factor-like domain 7
Radioimmunotherapy of solid tumors remains a challenge despite the tremendous success of 90Y ibritumomab tiuxetan (Zevalin) and 131I Tositumomab (Bexxar) in treating non-Hodgkins lymphoma. For a variety of reasons, clinical trials of radiolabeled antibodies against solid tumors have not led to responses equivalent to those seen against lymphoma. In contrast, promising responses have been observed with unlabeled antibodies that target solid tumor receptors associated with cellular signaling pathways. These observations suggest that anti-tumor efficacy of the carrier antibody might be critical to achieving clinical responses. Here, we review and compare tumor antigens targeted by radiolabeled antibodies and unlabeled antibodies used in immunotherapy. The review shows that the trend for radiolabeled antibodies under preclinical development is to also target antigens associated with signaling pathways that are essential for the growth and survival of the tumor.
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